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Tsung-Han Chou, Giovanni Luca Romano, Rosario Amato, Vittorio Porciatti; Nicotinamide-rich diet in DBA/2J mice preserves RGC metabolic function as assessed by PERG adaptation to flicker.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):639.
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© ARVO (1962-2015); The Authors (2016-present)
Flickering light around 10 Hz increases metabolic demand and induces vasodilation in the inner retina. Flicker also causes marked reduction of the PERG signal (adaptation) in healthy mice (PMID: 31804570). We tested whether flicker-induced PERG adaptation is altered with age in DBA/2J (D2) mouse glaucoma and whether it is preserved in D2 mice fed with vitamin B3-rich diet, which supports mitochondrial function and has neuroprotective action on RGC (PMID: 28209901).
Pre-glaucomatous D2 mice were fed with either standard chow (control, N=5) or with chow and water enriched with Nicotinamide (NAM, 2000 mg/kg per day) (treated, N=5). All mice were longitudinally tested with PERG with superimposed square-wave flicker at 101 Hz (baseline) followed by PERG with superimposed flicker at 11 Hz (test). Flicker PERG adaptation was defined as the percent amplitude change upon transition from 101 Hz flicker to 11 Hz flicker. At 13 months, flat-mounted retinas were processed for RGC immunostaining (RBPMS and mito-tracker).
In 3-month D2 mice, the mean amplitude of baseline PERG+101Hz flicker was about 11 µV and that of the test PERG+11Hz flicker was 6.5 µV (41% adaptation). With increasing age, both the PERG+101Hz flicker and the PERG+11Hz flicker decreased, however with a shallower slope in NAM-treated mice compared to controls (GEE statistics, P<0.01) resulting in preserved adaptation (17.5% vs. 0%) at endpoint (12 months). Compared to controls, the NAM-treated group had higher RGC density (~5x), larger RGC soma size (2x), and greater intensity of mitochondrial staining (~2x). The magnitude of PERG adaptation to flicker was significantly (P<0.05) correlated with the intensity of mitochondrial staining within RGCs.
Rescue of functional RGC in aged D2 mice fed with NAM-rich diet is consistent with previous reports. The present results show that flicker PERG adaptation - an index of autoregulation in response to increased metabolic demand - is reduced in D2 glaucoma and is preserved in D2 fed with NAM-rich diet. The magnitude of flicker-PERG adaptation is associated with the intensity of mito-tracker immunostaining. Flicker-PERG adaptation may provide a tool for investigating neurometabolic coupling in mouse models of optic nerve disease.
This is a 2020 ARVO Annual Meeting abstract.
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